Indomethacin treatment slows disease progression and enhances a Th1 response in susceptible BALB/c mice infected with Leishmania major

Parasite Immunol. 1999 May;21(5):273-7. doi: 10.1046/j.1365-3024.1999.00211.x.

Abstract

Prostaglandins of the E series inhibit the development of Th1 responses. When infected with Leishmania major, BALB/c mice fail to develop a Th1 response, but instead mount a Th2 response and die of the disease. Therefore, we treated L. major-infected BALB/c mice with indomethacin, which inhibits prostaglandin production. Indomethacin lessened disease severity (parasite burden and pathology), and promoted a Th1 response, but the mice still succumbed to infection. The explanation for these observations may be two-fold: (1) the beneficial effects of indomethacin were predominantly observed later in infection (beyond two weeks), a time at which indomethacin was unable to sufficiently block the development of a Th2 response; (2) indomethacin was unable to induce a Th1 response in BALB/c mice that was of the same magnitude as the Th1 response observed in C57BL/6 mice infected with L. major.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiprotozoal Agents / therapeutic use*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Disease Progression
  • Female
  • Immunity, Cellular
  • Indomethacin / therapeutic use*
  • Leishmania major*
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leishmaniasis, Cutaneous / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Prostaglandin Antagonists / therapeutic use
  • Th1 Cells / immunology*

Substances

  • Antiprotozoal Agents
  • Cyclooxygenase Inhibitors
  • Prostaglandin Antagonists
  • Indomethacin